GLUT-1

• OMIM: 138 140
• UniProt: P11166

GLUT -1 and erythrocytes / brain hexose facilitators ( gene: SLC2A1 ), the protein in the cell membrane of the erythrocytes, and cells of the blood -brain barrier in mammals comprising the introduction of glucose, but also other pentoses and hexoses, as well as vitamin C facilitates the cell interior. It is a transport protein and it is essential to supply the brain with glucose. GLUT-1 but is also found in most other tissues, where it allows the supply of glucose independent of insulin. Mutations in the SLC2A1 gene may cause the GLUT1 deficiency syndrome.

Function

The transport equation is:

It is a uniport. Preferred solutes are D- glucose, dehydroascorbic acid, quercetin. Through a parallel channel can simultaneously diffuse water. For glucose transport, a slipping process over several binding sites has been suggested time. Switching to dehydroascorbate transport in erythrocytes by means of the membrane protein stomatin and this process occurs only in those mammals that can not themselves form ascorbic acid.

Medical importance

In animal models of diabetes mellitus, the expression of GLUT1 is reduced in myocardial tissue and vessels in the retina ( retina). Patients with diabetes mellitus type 2 in skeletal muscle cells have a decreased expression of GLUT1 and decreased glucose uptake. In sharp contrast, in diabetic patients in the Mesangiumzelle the renal corpuscle increased expression of GLUT1. This results in the kidney an increased glucose uptake and an overactivation glucoseabhängier metabolic pathways. This ultimately leads to an increased production of TGF- β. This up-regulation of TGF- β promotes the excessive production of extracellular matrix which is considered to be a possible cause of diabetic renal injury. In addition, TGF- β in turn promotes the expression of GLUT1 and so maintains the pathomechanism.

An increased pressure in the capillaries of the renal corpuscle or an increase of angiotensin II also stimulates the expression of GLUT1 in the kidney. Possibly, this mechanism is a cause of high blood pressure or obesity renal impairment ( nephrosclerosis ).

A congenital defect in the SLC2A1 gene may cause GLUT1 deficiency ( GLUT1 deficiency syndrome). It results due to a lack of supply of the brain with glucose as the sole fuel to a significant delay in physical and mental development, epilepsy and a back constant growing head circumference ( acquired microcephaly ), in about half of affected children also to an impaired balance (ataxia) and decreased muscle strength ( muscle hypotonia ).

GLUT-1 has a docking point for the HTLV. Variants of GLUT -1 are associated with diabetic nephropathy in diabetes mellitus. GLUT-1 is overexpressed in several cancer cell lines.

Regulation

In the regulation of glucose uptake and the expression of GLUT-1, GSK -3 is obviously involved, via modulation by TSC2 and mTOR.